ACTG 384 is a six-arm double blinded study designed to examine the optimal initial regimen in antiretroviral-naive subjects (with plasma HIV-1RNA levels >500 copies/ml.) using 3-or-4 drug regimens. Sequential triple combination therapy (Arms A,B,C,D) will be evaluated in subjects who fail initial therapy by assigning the subject to a regimen that includes a different double necleoside analog reverse transcriptase inhibitors (NRTIs) with efavirenz (EFV) or nelfinavir(NFV), whichever they were not receiving. Two 4-drug regimens containing double NRTIs with both EFV and NFV will also be evaluated. A major effort will be made to examine pharmacologic and adherence factors, as well as virologic and immunologic factors, that may contribute to virologic failure. The design of ACTG 384 allows the opportunity to examine subjects receiving two consecutive antiretroviral regimens, and for four of the six arms, a third salvage regimen.